cml treated with bosutinib after relapse

Conditions: Chronic Myeloblastic Leukaemia

Summary: prospective, open label, multicenter, phase ii study evaluating correlation of snps with efficacy and toxicity in patients treated with bosutinib. a total of 50 patients with previously treated ph+ chronic phase cml will be included in the study


Eligibility criteria:
inclusion criteria: * signed and dated informed consent form. * patients with chronic ph + cml who presented a non-optimal response at 3 months prior to itk treatment (imatinib, nilotinib, dasatinib). it is defined as a non-optimal response: bcr-abl\> 10% per qrt-pcr (is) at 3 months of initiation of treatment. bcr / abl ≥ 1% per qrt-pcr (is) at 6 months of initiation of treatment. bcr / abl\> 0.1% qrt-pcr (is) at 12 months of initiation of treatment. bcr-abl1\> 0.1% qrt-pcr (is) at any time after 12 months of treatment initiation. * ecog performance status of 0 or 1. * recovery at grade 0-1, or at the baseline value of any pretreatment toxicity, except for alopecia. cases with significant toxicity will be analyzed individually by the study coordinators * able to take daily oral capsules * adequate bone marrow function: 1. absolute neutrophil count \> 1000/mm3 (\>1000 x109/l) 2. platelets ≥ 100,000/mm3 (\>100 x109/l) 3. absent any platelet transfusions during the preceding 14 days. * adequate hepatic, and renal function: * ast/alt ≤ 2.5 × upper limit of normal (uln) or ≤ 5 × uln if attributable to liver involvement of leukemia * total bilirubin ≤ 1.5 × uln * creatinine ≤ 1.5 × uln * age \> 18 years * willingness of male and female subjects, who are not surgically sterile or postmenopausal, to use reliable methods of birth control (oral contraceptives, intrauterine devices, or barrier methods used with a spermicide) for the duration of the study and for 30 days after the last dose of bosutinib. exclusion criteria * subjects with philadelphia chromosome and bcr-abl negative cml. * overt leptomeningeal leukemia. subjects must be free of cns involvement for a minimum of 2 months. subjects with symptoms of cns involvement must have a diagnostic lumbar puncture prior to study enrollment. * subjects with extramedullary disease only. * prior stem cell transplantation. * major surgery within 14 days or radiotherapy within 7 days before the first dose of bosutinib (recovery from any previous surgery should be complete before day 1) * a history of a clinically significant ventricular arrhythmia, congenital or acquired prolonged qt interval, a baseline qtcf \> 0.47 sec (average of triplicate readings) or unexplained syncope, uncontrolled or symptomatic congestive heart failure (chf) within 3 months, or myocardial infarction (mi) within 6 months. * concomitant use of or need for medications known to prolong the qt interval * uncorrected hypomagnesemia or hypokalemia due to potential effects on the qt interval * recent (within 30 days of study entry) or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, short bowel syndrome, bleeding, or grade \>1 diarrhea, nausea or emesis lasting more than 2 days, despite adequate medical therapy) * pregnant or breastfeeding women * evidence of serious active infection, or significant medical or psychiatric illness * known seropositivity to hiv, or current acute or chronic hepatitis b or hepatitis c (antigen positive), cirrhosis, hypokalemia (any grade), or clinically significant abnormal laboratory finding that would, in the investigator's judgment, make the subject inappropriate for this study.

Keywords: chronic myeloblastic leukaemia